Session Information

Background/Purpose: A novel multi-biomarker disease activity (MBDA) score has been validated and is a tool for monitoring disease activity in RA.1 Here, we evaluate the relationship between MBDA scores and both clinical and MRI assessments in patients (pts) from the ASSET trial (NCT00420199) who received abatacept (ABA) or placebo (pbo). Methods: Fifty pts with active RA, baseline (BL) DAS28-CRP >3.2 or Tender Joint Count and Swollen Joint Count >6 and CRP >upper limit of normal and inadequate response to MTX were randomly assigned 1:1 to receive ABA or pbo plus MTX, administered intravenously at BL; Days 15, 29; and every 28 days up to and including Day 113.2 Concentrations of 12 serum biomarkers including inflammatory cytokines and receptors (IL-6, TNF-RI), growth factors (EGF, VEGF-A), matrix metalloproteinases (MMP-1, MMP-3), skeletal-related protein (YKL-40), hormones (leptin, resistin), acute phase proteins, and markers of systemic inflammation (CRP and SAA1) were measured in pt serum at BL, 2 and 4 wks to calculate MBDA scores between 1 and 100. Disease activity measures (DAS28-CRP) were evaluated at BL, Wks 2 and 4, and every 4 wks until Wk 16, EULAR response was assessed at Week 16, and OMERACT RAMRIS scores (components: erosion, osteitis, and synovitis scores) were evaluated at BL and Mth 4. Associations between MBDA scores and DAS28-CRP, and between MBDA scores and OMERACT RAMRIS scores, were evaluated post hoc using Spearman’s rank correlation. The relationships of early changes in DAS28-CRP and MBDA score with subsequent EULAR response were evaluated by two-sample t-test. Comparisons of changes in disease activity scores between treatment arms were evaluated by two-sample t-tests. Results: Statistically significant correlations were observed between DAS28-CRP and MBDA score (r=0.47, p<0.001, n=146; all time points combined), and between change in DAS28-CRP and change in MBDA score from BL to Wk 4 (r=0.58, p<0.001, n=48). Pts in the ABA + MTX arm experienced significantly greater improvements in MBDA score and DAS28-CRP versus pbo + MTX arm at Wk 4 (p=0.003 in each case). A significant association between change in DAS28-CRP from BL to Wk 4 and EULAR good response at Wk 16 (p=0.02) was observed, as well as a marginally significant association between change in MBDA at Wk 4 and good EULAR response at Wk 16 (p=0.05). There was a significant correlation between MBDA score and OMERACT RAMRIS synovitis and osteitis scores at BL (Table).

Conclusion: In the ASSET trial, pts receiving abatacept had a better improvement in both clinical disease activity and disease activity biomarkers than pts in the pbo group. The MBDA score was correlated with disease activity and the OMERACT RAMRIS synovitis and osteitis scores. Monitoring of changes in MBDA score may be useful in RA pts in combination with clinical assessment.